Prostate cancer (CaP) is a major and growing health problem in America. During the past ten years, a 63% increase in the detection of CaP has occurred, with 122,000 cases currently detected annually. Due to the aging of the American male and intensified screening procedures, this figure win only continue to rise. Annually, there are 30,000 deaths attributed in American to CaP. The overall goal of this program project is the biological characterization of CaP which will allow individualized treatment of this disease. Information obtained in this program project should identify which patients with local disease need to be treated, determine when treatment should be initiated, and decide which therapy is most appropriate. Our hypothesis is that genetic abnormalities will be found at either the RNA or DNA level that determine the natural history of CaP. Studies will be conducted to identify and assess the prevalence of these genetic abnormalities or their manifestation in benign, premalignant, and malignant prostate tissue. By comparing the findings in local and metastatic tumors, characteristics of tumors with metastatic potential will be identified. By comparing the tumors that respond to radiation therapy and those that fail to respond, guidelines for selecting this form of therapy will become available. Similarly, for patients with disseminated CaP, the local and metastatic tumor will be compared at the time of initiating hormonal therapy and at the time of hormonal failure in order to evaluate the ability to predict these events by analysis of the human androgen receptor. The information gained will be compared and contrasted to the findings in patients with localized disease. The identified differences will allow classification of tumors into high and low metastatic potential groups. The program will include the standard staging and pathological information as well as urinary PSA studies, ploidy studies by flow and image analysis, and morphometric studies by image analysis. Molecular studies will focus on hAR, nm23, p53, and Rb-1 expression. The studies will be carried out under three separate projects: the flow and molecular studies at Davis, the image studies in Colorado. Tissue for these studies will come from Davis, St. Joseph Mercy Hospital, and Howard University. Thus, while each laboratory will produce its separate set of results, all studies will be accomplished on the same tissue obtained from closely characterized patients. The results will be centralized so that maximum information will be obtained in the most effective manner possible.